A randomized placebo-controlled trial is proposed of long term weekly iron and folic acid supplementation among young non-pregnant nulliparous women (<25 years) living in rural villages of Nanoro, Burkina Faso, an area with high malaria burden. This is a large Demographic Surveillance area of the Centre Muraz (population 52,000). The aim of the study is to test the hypothesis that iron supplementation in young women prior to conception and during early pregnancy results in reduced iron deficiency and anemia in pregnancy without increasing malaria risk. The primary end-point is prevalence of malaria parasitaemia at a first standardized antenatal visit (13-16 weeks gestation). Secondary outcomes for the pregnant and no pregnant cohorts include incidence of clinical malaria and prevalence of iron deficiency and anemia. Qualitative studies will assess adherence to weekly iron supplementation. A sample of 850 nulliparous pregnancies is required to assess clinically important differences in the primary outcome measure between the intervention and placebo groups. We anticipate this sample being generated from an eligible population of approximately 2000 non-pregnant women who will be followed from enrolment through conception to their first antenatal visit and delivery. After consent and recruitment each subject will receive their allocated intervention daily for 18 months or until conception and subsequent presentation for antenatal care. Study endpoints will be measured at first antenatal visit and delivery. Analysis will be based on intention to treat. An interim analysis of malaria prevalence in the non-pregnant cohort will be assessed in a cross-sectional survey during the first wet season of the follow-up period. The trial is designed to assess the safety of a weekly iron supplementation intervention specifically in terms of malaria morbidity and information on health care attendances will be monitored through weekly active surveillance. The trial will be conducted according to the principles of Good Clinical Practice. PUBLIC HEALTH RELEVANCE: Preventive iron and folate supplementation in women of reproductive age is widely promoted to reduce anemia prevalence. A weekly supplementation strategy for all women of child-bearing age is an innovative approach recently recommended by WHO. As malaria prevalence peaks at 13-16 weeks gestation it is essential to assess the safety of this approach in terms of early pregnancy malaria risk in women receiving long-term supplementation.